Specific aims 1. Definition of the sequence of events required for mucosal transmission at different portals of entry 2. Characterization of the viral determinants of mucosal transmission. 3. Definition of the earliest mucosal and systemic immune responses (adaptive and innate) following mucosal infection 4. Identification of genetic and protein biomarkers of resistance against HIV-1 transmission 5. Determine the role of immunological selection in shaping a distinct viral quasispecies that is sexually transmitted? 6. Determine whether systemic or mucosal vaccination can alter the dynamics of mucosal immune responses.